ANTIOXYURID ACTIVITY, TOXICOLOGY AND PATHOLOGY IN LABORATORY ANIMALS OF A CYANINE DYE [6-DIMETHYLAMINO-2-[2-(2,5-DIMETHYL-1-PHENYL-3-PYRRYL)VINYL]-1-METHYL-QUINOLINIUM CHLORIDE]

¹ The Research Laboratories, Parke, Davis and Company, Detroit, Michigan

1. Compound #715 was highly effective in well-tolerated (doses by the drug diet method against natural pinworm infections of mice and rats and against experimental infections of Strongyloides ratti in rats, hut was less effective against these infections when given by gavage. In tests by the (drug diet method for 6 days against Syphacia obvelata and Aspiculuris tetraptera of mice the respective ED₅₀'s were approximately 2.75 and 9.6 mgm. kgm./day. Thus #715 was approximately 40 and 5 times, respectively, as active as gentian violet against the two species of worms. The drug compared favorably with gentian violet in the other tests of ant helmintic action.

2. Rodent acute oral toxicity studies resulted in LD₅₀'s of 7.9 mgm. kgm. for mice and 161 mgm. kgm. for rats.

3. Rodent chronic oral toxicity tests over a 4-week periodi showed mice tolerate a maximum of 18 mgm./kgm. day by the drug diet method (0.0125 per cent diet concentration) and rats tolerate a maximum of 52 mgm. kgm. day (0.0625 per cent. concentration). However, the rats receiving this dose gained only as much weight as parallel controls.

4. Dogs tolerated 10-40 mgm./kgm. twice daily, 5 days per week for periods of 5-7 weeks without evidence of toxicity; doses of 40-80 mgm. kgm. twice daily for similar periods were associated with weight loss, vomiting, diarrhea and an occasional decrease in hemoglobin and numbers of erythrocytes, although the bone marrow apparently remained unaffected.

5. Pathologically, #715 administration was associated with mild to moderate irritation of the small intestine and mild degrees of liver and kidney damage; these signs occurred primarily at the higher chronic dose levels in both dogs and rodents and appeared to be reversible. Two rats on chronic administration at grossly toxic levels showed severe bone marrow hypoplasia. However, no evidence of this effect was detected in numerous other rats on lower dose levels or in dogs.

6. The possible usefulness of #15 in human oxyuriasis is considered.